Journal
JOURNAL OF NEUROVIROLOGY
Volume 25, Issue 2, Pages 150-161Publisher
SPRINGER
DOI: 10.1007/s13365-018-0696-3
Keywords
Galectin-9; HIV; Biomarkers; Neuroinflammation; Cognitive disorders
Categories
Funding
- National Institutes of Health (NIH) [1R01MH112457-01, U54NS43049, MH098759, R01 NS094067, P01 DA026134]
- Swedish State support for Clinical Research [ALFGBG-717531]
- NIH through Texas NeuroAIDS Research Center [U24MH100930]
- NIH through California NeuroAIDS Tissue Network [U24MH100928]
- NIH through National Neurological AIDS Bank [U24MH100929]
- NIH through Manhattan HIV Brain Bank [U24MH100931]
- NIH through Data Coordinating Center [U24MH100925]
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We previously reported that galectin-9 (Gal-9), a soluble lectin with immunomodulatory properties, is elevated in plasma during HIV infection and induces HIV transcription. The link between Gal-9 and compromised neuronal function is becoming increasingly evident; however, the association with neuroHIV remains unknown. We measured Gal-9 levels by ELISA in cerebrospinal fluid (CSF) and plasma of 70 HIV-infected (HIV+) adults stratified by age (older >40years and younger <40years) either ART suppressed or with detectable CSF HIV RNA, including a subgroup with cognitive assessments, and 18 HIV uninfected (HIV-) controls. Gal-9 tissue expression was compared in necropsy brain specimens from HIV- and HIV+ donors using gene datasets and immunohistochemistry. Among older HIV+ adults, CSF Gal-9 was elevated in the ART suppressed and CSF viremic groups compared to controls, whereas in the younger group, Gal-9 levels were elevated only in the CSF viremic group (p<0.05). CSF Gal-9 positively correlated with age in all groups (p<0.05). CSF Gal-9 tracked with CSF HIV RNA irrespective of age (=0.33; p<0.05). Higher CSF Gal-9 in the older viremic HIV+ group correlated with worse neuropsychological test performance scores independently of age and CSF HIV RNA (p<0.05). Furthermore, CSF Gal-9 directly correlated with myeloid activation (CSF-soluble CD163 and neopterin) in both HIV+ older groups (p<0.05). Among HIV+ necropsy specimens, Gal-9 expression was increased in select brain regions compared to controls (p<0.05). Gal-9 may serve as a novel neuroimmuno-modulatory protein that is involved in driving cognitive deficits in those aging with HIV and may be valuable in tracking cognitive abnormalities.
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